If an organ receives a physical trauma, such as an injury, surgery, a burn or an electric shock, or experiences inflammation as a result of a pathogenic cause, one of the inevitable consequences of the healing and inflammatory processes, which follow, is the formation of scar tissue. Scar tissue is formed as a result of the formation of a fibrin-platelet network following physical trauma or pathogenic inflammation, and the subsequent rebuilding and replacement of this network by granulation tissue.
The complex and typically highly irregular structure of the fibrin-platelet network, formed at an early stage after the trauma or as a result of inflammation, is of key importance in the fate of any wound healing process. Any physical structure, particularly filaments and membranes, whether diffusely or distinctly outlined, acts as a guide for the invading granulation tissue. This newly formed tissue is, in accordance with the mechanism described above, eventually rebuilt as scar tissue, organized is fibrous strands or membranes. The invading granulation tissue cells can practically never fully substitute for the original cells and, as a result, the tissue is never regenerated, but merely repaired. This is true for both the skin and for mucosal membranes, including those lining the body cavities, as well as other structures including muscles, tendons and nerves. Moreover, the scar tissue so formed may, in time, contract and remain contracted, deforming and disorganizing the injured area.
The proliferation and invasion of fibrin threads by even a few granulation tissue cells (including angiogenic cells) is usually sufficient to induce the formation of adhesions. The direction, density and organization of the individual fibrin threads in the fibrin-platelet network of the clot provides information, and determines the track to be taken by the invading granulation tissue cells, as well as by specific cells such as Schwann cells. Extracellular fibrin may deposit, stick to and establish abnormal bridges between adjacent structures. Thus, the structure of the fibrin-platelet network is of key importance in guiding the invading granulation tissue and thus in the formation of scar tissue.
Notwithstanding considerable literature on modalities of prevention of scar formation and removal of formed scar which have included the use of pressure dressings, splints, the application of silicone gel, steroid injections, protective devices, stretching devices, blood byproducts, protein solutions, gauzes, bandages, tapes and radiotherapy but all have had limited success and at times unwanted side effects.
Several patents have been granted for compositions claiming to prevent or treat human tissue scar formation, use of cactus and phellodendri. The following is a summary of some patents relevant to the invention described here.
European Patent Application EP 0 051 354 describes a polymeric substrate coated with the polysaccharide chitosan, to which is appended the antithrombotic agent heparin.
The U.S. Pat. No. 5,116,824 describes a composite material comprising an N-acylchitosan and collagen, which is suitable for, wound dressings. Heparin may be incorporated as an antithrombotic agent.
The U.S. Pat. No. 6,159,494 to Widgerow, et al., describes a method whereby postoperative scars are treated by a method of applying a microporous paper tape to the scar running along the length of the scar. A contact medium is applied to the exposed surface of the tape and penetrates to the skin. The contact medium comprises an expressed gel from the plant Bulbine frutescens and may contain asiaticoside and panthenol.
The U.S. Pat. No. 6,120,520 to Saadat, et al., is for an apparatus and methods for stimulating revascularization and tissue growth having a directable end region carrying a tissue piercing end effector. The apparatus optionally includes electrodes for depositing RF energy to form a controlled degree of scar tissue formation, means for delivering a controlled amount of a bioactive agent at the treatment site, or both.
The U.S. Pat. No. 6,127,348 to Roufa, et al., comprises the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions.
The U.S. Pat. No. 6,110,459 to Mickle, et al., is for a method is provided for forming a graft in heart tissue which comprises the transplantation of cells chosen from cardiomyocytes, fibroblasts, smooth muscle cells, endothelial cells and skeletal myoblasts.
The U.S. Pat. No. 6,093,388 to Fergusons is for treating fibrotic disorders using mannose-6-phosphate composition.
The U.S. Patent to Sawyer, et al., is for the inhibitors, obtainable from tissue or secretions of leeches typically of the order Rhynchobdellida to include the treatment of Crohn""s disease, tumor implantation, atherosclerosis, thrombotic microangiophathy, fibrous growths of the skin, acne, scar formation, membranous glomerulonephrits, cataracts, or infection with microfilarial nematodes.
The U.S. Pat. No. 5,994,325 to Roufa, et al., relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery that anionic polymers effectively inhibit invasion of cells associated with detrimental healing processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion correlates with the anionic charge density of the polymer.
The U.S. Pat. No. 5,981,606 to Martin pertains to invention of therapeutic TGF-beta-wound healing compositions for reducing the formation of scar tissue and increasing the proliferation and resuscitation rate of mammalian cells using pyruvate, an antioxidant and a mixture of saturated and unsaturated fatty acids and TGF-beta (GF) to form TGF-beta-wound healing compositions (ILAxe2x88x92D+GF). This invention also pertains to methods for preparing and using the TGF-beta-wound healing compositions.
The U.S. Pat. No. 5,919,476 to Fischer, et al., is for a bandage in the form of a reinforced silicone gel sheet for the treatment of scar tissue.
The U.S. Pat. No. 5,902,609 to Lee is for an invention that pertains to a composition for controlling wound scar production containing a calcium antagonist and a protein synthesis inhibitor.
The U.S. Patent to Fabo U.S. Pat. No. 5,891,076 is for a hypertrophic scar dressing that includes silicone-gel on that side of the dressing, which lies against the user""s skin when worn.
The U.S. Pat. No. 5,885,982 to Dolynchuk, et al., is for a method of treating or preventing hypertrophic scar tissue in human skin comprising applying topically an effective amount of a non-toxic amine compound that is a transglutaminase inhibitor having a free amino group is disclosed. The amine compound that is a transglutaminase inhibitor is also selective for inhibiting Type III collagen peptide cross-linking.
The U.S. Pat. No. 5,885,581 to Massand is for a dermatological composition for use in improving the appearance of scars comprising 20-30 parts by weight of polyethylene glycol 200, 0.005-0.03 parts by weight of preservative, 0.05-0.2 parts by weight of sorbic acid, 0.5-2 parts by weight of allantoin, 1-3 parts by weight of xanthan gum, 5-15 parts by weight of fluid onion extract (Extract Allium Cepa), dermatologically acceptable aqueous carrier 55-65 parts by weight.
The U.S. Pat. No. 5,789,445 to Schweiger is for a topical application of benzoyl perioxide to regions of tissue scarring of a composition comprising several ingredients commonly used in cosmetic products for reduction and a softening of scar tissue.
The U.S. Pat. No. 5,736,508 to McMichael is for methods to eliminate or reduce the appearance of scar tissue by administration of streptolysin O.
The U.S. Pat. No. 5,731,298 to Reinmuller is for a pharmaceutical composition for non-topical wound, scar and keloid treatment is described which contains cross-linked glycosaminoglycans and conventional pharmaceutical auxiliary and/or carrier substances. The pharmaceutical composition is preferably administered intralesionally e.g. by injection in the form of a gel containing water. The cross-linked glycosaminoglycans are also suitable for use as cosmetics and skin care products.
The U.S. Pat. No. 5,686,425 to Lee is for a composition and method that are effective in revitalizing scar tissue by introducing a bioactive substance having angiogenic activity into the scar tissue. The bioactive substance can be introduced by itself, or it can be introduced into the scar tissue in a timed-release form. The present invention is effective in treating stress urinary incontinence or localized muscular dysfunction.
The U.S. Pat. No. 5,662,904 to Ferguson et al., is for a composition for use in the treatment of wounds to inhibit scar tissue formation during healing, comprising an effective amount of an activity-inhibiting growth factor neutralizing agent or agents specific against all TGF-beta, except for TGF-beta..sub.3, and PDGF, together with a pharmaceutically acceptable carrier.
The U.S. Pat. No. 5,569,678 to Lee pertains to a method for controlling wound scar production by administering a calcium antagonist, alone or in a combination with or followed by a steroid, to the wound site.
The U.S. Pat. No. 5,555,162 to Lee is for a method for improving the size and appearance of a scar associated with a fibromatosis, a keloid, or a hypertrophic wound healing disorder comprises stimulating collagenase activity in the scar. Preferably, stimulating collagenase activity is accomplished by covering said scar with a thermal insulating material that elevates the surface temperature of the scar.
The U.S. Pat. No. 5,532,275 to Grumet is for treating wounds that is based on the system and/or topically administration of an effective amount, of para-amino benzoic acid or its derivatives.
The U.S. Pat. No. 5,520,926 to Ferguson is where mannose-6-and 1-phosphates and their pharmaceutically acceptable salts and bioprecursors thereof are useful in the treatment of fibrotic disorders.
The U.S. Pat. No. 5,194,248 to Holick is for providing vitamin D analogs to an individual with topical compositions comprising tachysterol and luministerol analogs are disclosed. Optionally, the compositions may comprise one or more sunscreen agents. Also disclosed are methods for treating decubitus or diabetic foot ulcers; ulcerative keratitis; psoriasis; wounds; and inhibiting scar formation by administering the pharmaceutical compositions comprising tachysterol or lumisterol analogs.
The U.S. Pat. No. 5,128,375 to Tanaka, et al., is a keloid treating agent comprising as an active ingredient ethanolamine or a pharmaceutically acceptable salt thereof which is useful for the treatment of keloid such as ture keloid, cicatrical keloid, hypertrophic scar, etc.
The U.S. Pat. No. 4,865,031 to O""Keefe is for a mesh like fabric for implantation beneath or within the dermis to control formation of scar tissue.
The U.S. Pat. No. 4,839,159 to Winter, et al., provides a composition comprising L-carnitine in a suitable vehicle for topical application in improving or healing skin conditions including wrinkling, dry or peeling skin, and burns (particularly sunburn), and in healing and prevention of scar formation, particularly that caused by infection by a pathogen.
The U.S. Pat. No. 4,772,591 to Meisner is for a method comprising administration of ascorbic acid, a source of biologically available calcium, a precursor or stimulant of epinephrine or nor-epinephrine selected from tyrosine and phenylalanine, and an anti-inflammatory substance selected from anti-inflammatory sugars, amino sugars and biocompatible acid addition salts thereof, and anti-inflammatory amino acids to treat or reduce or tissue degenerative effects of the inflammation associated with the natural wound healing process and promotes connective tissue (scar tissue) growth in the wound.
The U.S. Pat. No. 4,694,021 to Schweiger is for topical application to regions of tissue scarring of a composition comprised of several ingredients commonly used in cosmetic products, such as urea, which leads to a reduction and a softening of scar tissue.
The U.S. Pat. No. 6,174,855 to Hansson provides the use of a thrombin inhibitor in the manufacture of a product for use in the control of wound healing processes within the body, in particular, the inhibition or prevention of fibrin-related adhesion and/or scar tissue formation, as well as products for use in the control of wound healing processes within the body comprising polysaccharides (e.g., chitosans) and low molecular weight peptide-based thrombin inhibitors.
The U.S. Pat. No. 5,736,584 to Kunkel is for an insect repelling composition comprising mineral oil cactus extract made from the leaves and stem of the Prickly Pear cactus.
The U.S. Pat. No. 5,747,462 to Feuntes relates to the area of pharmacology; its objective is to solve the technical problem of inflammation, pain, pruritus and local hyperthermia in human beings and animal species. The composition and the subcompositions thereof are obtained from plants of the family Cactaceae the main methodological steps being a set of processes; production, purification, physicochemical quantification, biotherapeutic evaluation, biopharmaceutical formulation and molecular identification. From the molecular identification a set of molecules is recognized, comprising carbohydrates and an aromatic amine.
The U.S. Pat. No. 6,039,954 to Yu, et al., is for herbal compositions containing for the treatment of gastrointestinal disorders, in particular Irritable Bowel Syndrome (IBS). The compositions are formulated preferably with powdered herbs including phellodendri.
The U.S. Pat. No. 5,916,555 to Lee, et al., is for a pharmaceutical composition containing a combination of natural drugs for treatment of diabetes. More specifically, the present invention relates to a composition containing 17 kinds of main natural drugs, i.e. Cordyceps, Bezoar bovis, Carthami flos, Astragali radix, Hirudo, Polygoni cuspidati radix, Polygonati falcati rhizoma, Euonymi lignum suberalatum, Corni fructus, Moutan cortex, Lycii cortex radicis, Lycii fructus, Atractylodis rhizoma alba, Atractylodis rhizoma, Coptidis rhizoma, Puerariae radix and Rehmaniae radix crudae. In addition to 17 kinds of main natural drugs, if desired, the composition of the present invention can contain one or more supplementary natural drugs selected from the group consisting of Liriopsis tuber, Cistanchis herba, Adenophorae radix, Salviae radix, Ginseng radix rubra, Anemarrhenae rhizoma, Pachymae fungus, Phellodendri cortex, Mori radicis cortex, Schizandrae fructus, Galli stomachichum corium, Trichosanthis radix, Rhei rhizoma, Dioscoreae rhizoma, Alisma rhizoma, Polygoni multiflori radix, Galla rhois, Formica fusca L., Sanchi ginseng, Margaritum and Gecko.
The U.S. Pat. No. 5,908,628 to Hou provides compositions comprising talc, silkworm excrement, and ingredients of plants of species of the genera Stephania, Coix, Pinellia, Prunus, Phellodendron, Sophora, Tetrapanax, Stemona, Glycyrrhiza, Tripterygium, Forsythia and Siegesbeckia, wherein such compositions have analgesic, antipyretic, and antiflammatory properties. The present invention also provides methods of using such compositions for treating various diseases, including osteoarthritis and rheumatoid arthritis.
The U.S. Pat. No. 5,405,608 to Xu relates to a pharmaceutical composition mainly used for treating thermal injuries of warm blooded mammals and human. It is composed of 3 to 15% by weight of beeswax and 85 to 97% by weight of sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule. In the sesame oil extract, each of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule is in an amount of 2 to 10 weight percent based upon the total weight of sesame oil.
The U.S. Pat. No. 5,344,648 to Haga, et al., is for a central nervous system activator comprising a body or a dried product of a plant belonging to Rutaceae, or an extraction product selected from the group consisting of a lower alkane insoluble portion thereof, a lower fatty acid ester extract of the lower alkane insoluble portion, a lower fatty acid ester-halogenated lower alkane soluble portion of the lower fatty acid ester extract, a limonin fraction of the lower fatty acid ester-halogenated lower alkane soluble portion, and an obacunone fraction of the lower fatty acid ester-halogenated lower alkane soluble portion and a central nervous system activator comprising a limonoid.
There is provided the use of a specific composition containing extract of two herbs, namely, Cortex Phellodendri (Huangbo or Amur Cork tree bark) and Opuntia ficus indica (Cactus), extracted by a specific method and combined in a specific proportion as a treatment of existing body scars or prevention of scar tissue formation in the control of wound healing processes. The composition described here can be used for any type of anticipated scarring such as in surgery or for the amelioration of pre-existing scars. The composition is used for a few weeks to a few months depending on the stage and maturity of the scar wound and leaves a cosmetically improved skin surface that is also more functional physiologically and mechanically. The preferred composition described here contains only natural ingredients that have been proven safe for consumption by humans and animals.